TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16638	50137;50138;50139	chr2:178612809;178612808;178612807	chr2:179477536;179477535;179477534
N2AB	14997	45214;45215;45216	chr2:178612809;178612808;178612807	chr2:179477536;179477535;179477534
N2A	14070	42433;42434;42435	chr2:178612809;178612808;178612807	chr2:179477536;179477535;179477534
N2B	7573	22942;22943;22944	chr2:178612809;178612808;178612807	chr2:179477536;179477535;179477534
Novex-1	7698	23317;23318;23319	chr2:178612809;178612808;178612807	chr2:179477536;179477535;179477534
Novex-2	7765	23518;23519;23520	chr2:178612809;178612808;178612807	chr2:179477536;179477535;179477534
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-8
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.5523
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/D	rs2056589440	None	0.997	N	0.683	0.109	0.216624796971	gnomAD-4.0.0	1.36967E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79993E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.2126	likely_benign	0.2517	benign	-0.448	Destabilizing	0.997	D	0.812	deleterious	N	0.475824495	None	None	N
E/C	0.8997	likely_pathogenic	0.931	pathogenic	-0.217	Destabilizing	1.0	D	0.728	deleterious	None	None	None	None	N
E/D	0.0893	likely_benign	0.1018	benign	-0.448	Destabilizing	0.997	D	0.683	prob.neutral	N	0.474441744	None	None	N
E/F	0.7802	likely_pathogenic	0.8399	pathogenic	-0.184	Destabilizing	1.0	D	0.72	deleterious	None	None	None	None	N
E/G	0.2834	likely_benign	0.3539	ambiguous	-0.665	Destabilizing	0.999	D	0.69	prob.delet.	N	0.470006594	None	None	N
E/H	0.6369	likely_pathogenic	0.7297	pathogenic	0.12	Stabilizing	1.0	D	0.557	neutral	None	None	None	None	N
E/I	0.3826	ambiguous	0.4402	ambiguous	0.097	Stabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
E/K	0.274	likely_benign	0.3696	ambiguous	0.198	Stabilizing	0.997	D	0.809	deleterious	N	0.475634262	None	None	N
E/L	0.3899	ambiguous	0.4533	ambiguous	0.097	Stabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
E/M	0.5167	ambiguous	0.5724	pathogenic	0.135	Stabilizing	1.0	D	0.732	deleterious	None	None	None	None	N
E/N	0.3088	likely_benign	0.3883	ambiguous	-0.237	Destabilizing	0.999	D	0.733	deleterious	None	None	None	None	N
E/P	0.5038	ambiguous	0.5724	pathogenic	-0.064	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
E/Q	0.2304	likely_benign	0.2752	benign	-0.179	Destabilizing	0.999	D	0.714	prob.delet.	N	0.472831984	None	None	N
E/R	0.4544	ambiguous	0.5765	pathogenic	0.499	Stabilizing	0.999	D	0.725	deleterious	None	None	None	None	N
E/S	0.2445	likely_benign	0.2988	benign	-0.389	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
E/T	0.3046	likely_benign	0.365	ambiguous	-0.207	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
E/V	0.2481	likely_benign	0.2957	benign	-0.064	Destabilizing	0.999	D	0.757	deleterious	N	0.468553738	None	None	N
E/W	0.9353	likely_pathogenic	0.9614	pathogenic	0.015	Stabilizing	1.0	D	0.727	deleterious	None	None	None	None	N
E/Y	0.6765	likely_pathogenic	0.7613	pathogenic	0.068	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.